Vença-Stastny/Getty Images
Vença-Stastny/Getty Images
A drug taken by millions of people to control diabetes could do more than lower blood sugar levels.
Research suggests that metformin has anti-inflammatory effects that may help protect against common age-related illnesses, including heart disease, cancer, and cognitive decline.
Scientists who study the biology of aging designed a clinical study, known as the TAME trial, to test whether metformin can help prevent these diseases and promote longer health spans in healthy older adults. .
Michael Cantor, an attorney, and his wife Shari Cantor, mayor of West Hartford, Connecticut, both take metformin. “I tell all my friends about it,” says Michael Cantor. “We all want to live a little longer and with a quality life if we can,” he says.
Michael Cantor started taking metformin about ten years ago, as his weight and blood sugar levels gradually increased. Shari Cantor started taking metformin during the pandemic after reading that it could help protect against serious infections.
Both Shari and Michael Cantor take metformin. They are both in their 60s and report feeling healthy and full of energy.
Thérèse Oberst/Michael Cantor
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Thérèse Oberst/Michael Cantor
Both Shari and Michael Cantor take metformin. They are both in their 60s and report feeling healthy and full of energy.
Thérèse Oberst/Michael Cantor
The Cantors are in their 60s and both say they feel healthy and have lots of energy. Both noticed improvements in their digestive systems – feeling more “regular” after starting the medication,
Metformin costs less than a dollar a day and, depending on insurance, many people pay no out-of-pocket cost for the drug.
“I don’t know if metformin increases people’s lifespan, but the existing evidence suggests that it very well could,” says Steven Austad, senior scientific adviser at the American Federation for Aging Research, which studies the biology of aging.
An old medicine with surprising benefits
Metformin was first used in France in the 1950s to treat diabetes. The drug is a derivative of guanidine, a compound found in rue de la Chèvre, a medicinal plant long used in Europe.
The FDA approved metformin for the treatment of type 2 diabetes in the United States in the 1990s. Since then, researchers have documented several surprises, including a reduction in cancer risk. “It was a bit of a shock,” Austad says. A meta-analysis including data from dozens of studies found that people taking metformin had a lower risk of several types of cancers, including gastrointestinal, urologic, and blood cancers.
Austad also points to a British study that found a lower risk of dementia and mild cognitive decline in people with type 2 diabetes taking metformin. Additionally, research indicates improved cardiovascular outcomes among people taking metformin, including a reduced risk of cardiovascular death.
As promising as that sounds, Austad says most of the evidence is observational, pointing only toward an association between metformin and risk reduction. The evidence fails to prove cause and effect. Additionally, it is unclear whether the benefits documented in people with diabetes will also reduce the risk of age-related diseases in healthy older adults.
“That’s what we need to understand,” says Steve Kritchevsky, a professor of gerontology at the Wake Forest School of Medicine who is one of the lead investigators in the Tame Trial.
The objective is to better understand the mechanisms and pathways by which metformin acts in the body. For example, researchers are studying how the drug can help improve cell energy by stimulating autophagy, which is the process of removing or recycling damaged elements inside cells.
Researchers also want to learn more about how metformin may help reduce inflammation and oxidative stress, which can slow biological aging.
“When there’s excess oxidative stress, it damages the cell. And that accumulation of damage is essentially what aging is,” Kritchevsky says.
According to Kritchevsky, when the forces that damage cells operate more quickly than the forces that repair or replace cells, it is called aging. And it’s possible that medications like metformin can slow this process.
By targeting the biology of aging, the hope is to prevent or delay several diseases, says Dr. Nir Barzilai of the Albert Einstein College of Medicine, who is leading the effort to launch the trial.
The ultimate in preventive medicine
In 2015, Austad and a group of aging researchers began pushing for a clinical trial.
“Many of us went to the FDA asking them to approve a metformin trial,” Austad recalls, and the agency was receptive. “If you could help prevent multiple problems at the same time, as we think metformin could do, then that’s almost the ultimate in preventative medicine,” Austad says.
The goal is to enroll 3,000 people aged 65 to 79 for a six-year trial. But Dr. Barzilai says it took time to get funding. “The main obstacle to funding this study is that metformin is a generic drug, so no pharmaceutical company is able to make money,” he says.
Barzilai reached out to philanthropists and foundations and made some pledges. The National Institute on Aging, part of the National Institutes of Health, has set aside about $5 million for the research, but that’s not enough to fund the study, which is estimated to cost between $45 million and $70 million. .
The frustration with the lack of funding is that if the trial finds protective effects, millions of people could benefit. “It’s something that everyone will be able to afford,” Barzilai says.
Currently, the FDA does not recognize aging as a treatable disease, but researchers hope this will mark the start of a paradigm shift – from treating each age-related medical condition separately to treating these conditions together. by targeting aging itself.
For now, metformin is only approved to treat type 2 diabetes in the United States, but doctors can prescribe it off-label for conditions other than its approved use.
Michael and Shari Cantor’s doctors were comfortable prescribing it to them, given the drug’s long safety history and possible benefits in delaying age-related illnesses.
“I walk a lot, I hike, and at 65 I have a lot of energy,” says Michael Cantor. I feel like metformin helps,” he says. He and Shari say they haven’t experienced any negative side effects.
Research shows that a small percentage of people who take metformin experience gastrointestinal upset that makes the drug intolerable. And some people develop a vitamin B12 deficiency. A study found that people over the age of 65 who take metformin might have a harder time growing new muscles.
“There is some evidence that people who exercise and take metformin gain less muscle mass,” says Dr. Eric Verdin, president of the Buck Institute for Research on Aging. “This could be a concern for undermuscled people.
But Verdin says it might be possible to repurpose metformin in other ways. “A number of companies are exploring metformin in combination with other drugs,” he says. He points to ongoing research into combining metformin with a drug called galantamine for the treatment of sarcopenia, the medical term for age-related muscle loss. Sarcopenia affects millions of older people, especially women.
The science of testing drugs targeting aging is advancing rapidly, and metformin is not the only drug capable of treating the underlying biology.
“No one thinks this is the be all and end all to drugs targeting aging,” Austad says. According to him, the data from the clinical trial could stimulate investments by large pharmaceutical companies in this area. “They could come up with much better drugs,” he says.
Michael Cantor knows there are no guarantees with metformin. “Maybe it doesn’t do what we think in terms of longevity, but it certainly won’t hurt me,” he says.
Cantor’s father had his first heart attack at age 51. He says he wants to do everything he can to prevent disease and live a healthy life, and he thinks metformin is a tool that could help him.
For now, Dr. Barzilai says the metformin clinical trial can start when the money arrives.
This story was edited by Jane…
News Source : www.npr.org
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